A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

Abstract

Synthesizing organocatalysts is often a long and cost-intensive process, therefore, the recovery and reuse of the catalysts are particularly important to establish sustainable organocatalytic transformations. In this work, we demonstrate the synthesis, application, and recycling of a new lipophilic cinchona squaramide organocatalyst. The synthesized lipophilic organocatalyst was applied in Michael additions. The catalyst was utilized to promote the Michael addition of cyclohexyl Meldrum’s acid to 4-chloro-trans-β-nitrostyrene (quantitative yield, up to 96% ee). Moreover, 1 mol % of the catalyst was feasible to conduct the gram-scale preparation of baclofen precursor (89% yield, 96% ee). Finally, thanks to the lipophilic character of the catalyst, it was easily recycled after the reaction by replacing the non-polar reaction solvent with a polar solvent, acetonitrile, with 91–100% efficiency, and the catalyst was reused in five reaction cycles without the loss of activity and selectivity.

Keywords

• baclofen
• catalyst recovery
• lipophilic cinchona squaramide
• organocatalysis
• stereoselective catalysis